I just finished listening to an interesting podcast featuring Dr. Zeisel, a researcher at the NC Nutrition Research Institute. The interview discussed the body’s need for choline and the impact of some genetic variants on our ability to produce it in the body. So I decided to dig into this a little more and look at some of the SNPs covered by 23 and Me or AncestryDNA data related to choline.
A little background information…
Choline is involved in several critical roles in the body including:
Recent studies of choline levels show:
Generally, people can make some choline in their liver. But some people have genetic variants that reduce their ability to make choline. They need to ensure adequate intake through food or supplements.
Choline is the precursor to acetylcholine, which is a neurotransmitter. Acetylcholine controls muscles, heart rhythm, and other function.
The FDA gives a recommended adequate intake for adults as 425-550 mg/day. [ref]
Your body’s need for choline from the diet will depend in part on how much folate you eat and how well your methylation cycle works. Choline acts as a methyl donor in the methylation cycle, and with low folate or decreased enzyme efficiency in the folate pathways, your choline requirement may increase.
PEMT – phosphatidylethanolamine N-methyltransferase
The PEMT pathway is responsible for the body’s production of phosphatidylcholine which is part of the phospholipid bilayer making up the membranes surrounding our cells. Note that 23andMe does not cover all of the SNPs in PEMT that are relevant to choline levels.
Check your genetic data for rs7946 (23andMe v4, v5)
CHKA – Choline kinase alpha
The choline kinase alpha enzyme is involved in the pathway of reactions that converts choline into phosphatidylcholine (for cell membranes). Choline kinase specifically is the catalyst in the reaction that converts choline into 0-phosphocholine. The variant below decreases the turnover of dietary methionine into choline. Carriers of the variant are more likely to need dietary choline since they don’t convert dietary protein (methionine) as well.
Check your genetic data for rs10791957 (23andMe v4, v5; AncestryDNA)
“Specifically, the variant appears to decrease the use of dietary choline for PEMT-PC synthesis relative to CDP-PC synthesis. Variant individuals displayed decreased turnover of choline-derived methionine → PEMT-PC over the study period, indicating decreased activity of PEMT relative to women without the variant, and also tended to exhibit lower relative PEMT-PC/CDP-PC enrichment as compared to non-variants.”[ref]
In another study, those with C/C (normal) were found to be “less likely to have clinical symptoms after consuming a low-choline diet.” [ref]
BHMT – Betaine-homocysteine S-methyltransferase
Check your genetic data for rs3733890: (23andMe v4, v5; AncestryDNA)
“Together, these results indicate that the variant favors the use of dietary choline for CDP-PC synthesis at the expense of betaine synthesis.” [ref]
FMO3 – Flavin-containing monooxygenase
Check your genetic data for rs2266782: (23andMe v4, v5):
“While a previous study from our group suggested that the variant might be associated with increased use of choline as a methyl donor in men (based on increased DMG pool size) , results from the present study, indicate that women with the variant actually use choline less as a methyl donor. Variant women tended to have a lower turnover of betaine → methionine over the study period. In addition, variant women exhibited a greater turnover of choline-derived methionine → PEMT-PC over the study period, which is consistent with previous findings from our lab that have identified lower methionine excretion among variant individuals (i.e., greater use of methionine may reduce excretion)” [ref]
MTHFD1 – methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1
This is actually an enzyme in the folate pathway, but it affects your need for adequate choline in the diet.
Check your genetic data for rs2236225 (G1958A): (23andMe v.4 and v.5)
Carriers of the A allele are more likely to have choline deficiency on a low choline diet (modified by folate intake) [ref] [ref] In one study with premenopausal women, those with an A-allele were 15 times more likely to show choline deficiency symptoms on a diet low in choline.
Food and supplements:
Excellent (egg-cellent :-) sources of choline in foods include: eggs, liver, shitake mushrooms, milk, and various meats. [ref] Raw egg yolks are a better source of choline than cooked, but there are drawbacks, especially if you don’t know the source of your eggs.
More to read:
Dr. Amy Yasko also has a lot of information about the role of choline in the methylation cycle. Her view is that MTHFR variants can be bypassed using choline if a person doesn’t have BHMT or PEMT variants. Her free book Companion Guide: Feel Good Nutrigenomics is a good place to start, and her full book Feel Good Nutrigenomics as well as videos, etc can be found on her website.